title: Temozolomide and 13-cis retinoic acid in patients with anaplastic gliomas: a prospective single-arm monocentric phase-II study (RNOP-05).
abstract: The objective of this prospective, monocentric phase-II pilot study was to evaluate toxicity and efficacy of neoadjuvant temozolomide (TMZ) and 13-cis retinoic acid (13-cRA) treatment in patients with newly diagnosed anaplastic gliomas after total or subtotal tumor resection. The primary endpoint of the study was median progression-free survival (PFS). Secondary endpoints were toxicity and PFS rates at 6, 12 and 24 months. Thirty-two adult patients were included in the study and treated with a median number of 10 TMZ and 13-cRA cycles (range 1-26). The majority of patients had favorable prognostic factors characterized by young age, complete resection, oligodendroglial histology, 1p/19q co-deletion, O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation and isocitrate dehydrogenase 1 (IDH1) mutation. Grade 3/4 myelotoxicity occurred in 5/32 patients, and about 90% of patients suffered from grade 2/3 adverse events attributable to 13-cRA. The median PFS was 37.8 months (95% CI 22.2-53.4). The 6-, 12- and 24-month PFS rates were 84.4, 75 and 42.4%. The extent of tumor resection was the only prognostic factor associated with better PFS. TMZ and 13-cRA treatment did not improve PFS when retrospectively compared to the TMZ-treated group within the randomized NOA-04 phase-III trial. In conclusion, 13-cRA addition to TMZ in a neoadjuvant setting showed acceptable toxicity, but did not yield an advantage in PFS in patients with newly diagnosed anaplastic gliomas after total or subtotal tumor resection.
authors.affiliation: Department of Neurology, University Medical Center Regensburg, Universitätsstrasse 84, 93053, Regensburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Grauer
authors.forename: Christina
authors.initials: C
authors.lastname: Pascher
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.forename: Florian
authors.initials: F
authors.lastname: Zeman
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Martin
authors.initials: M
authors.lastname: Proescholdt
authors.forename: Alexander
authors.initials: A
authors.lastname: Brawanski
authors.forename: Thorsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bogdahn
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004224:Diterpenes; D004334:Drug Administration Schedule; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011446:Prospective Studies; D012172:Retinaldehyde / Q000627:therapeutic use*; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D004224:Diterpenes; D025521:Tumor Suppressor Proteins; C031338:13-cis-retinal; D003606:Dacarbazine; D007521:Isocitrate Dehydrogenase; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D012172:Retinaldehyde; D000077204:Temozolomide